Liprotides made of α-lactalbumin and cis fatty acids form core-shell and multi-layer structures with a common membrane-targeting mechanism

TY - JOUR

T1 - Liprotides made of α-lactalbumin and cis fatty acids form core-shell and multi-layer structures with a common membrane-targeting mechanism

AU - Frislev, Henriette Kristina Søster

AU - Jessen, Christian M

AU - Oliveira, Cristiano L P

AU - Pedersen, Jan Skov

AU - Otzen, Daniel E

N1 - Copyright © 2016 Elsevier B.V. All rights reserved.

PY - 2016/7

Y1 - 2016/7

N2 - α-Lactalbumin (aLA) has been shown to form complexes with oleic acid (OA), which may target cancer cells. We recently showed that aLA and several other proteins all form protein-OA complexes called liprotides with a generic structure consisting of a micellar OA core surrounded by a shell of partially denatured protein. Here we report that a heat treatment and an alkaline treatment method both allow us to prepare liprotide complexes composed of aLA and a range of unsaturated fatty acids (FA), provided the FAs contain cis (but not trans) double bonds. All liprotides containing cis-FA form both small and large species, which all consist of partially denatured aLA, though the overall shape of the species differs. Small liprotides have a simple core-shell structure while the larger liprotides are multi-layered, i.e. they have an additional layer of both FA and aLA surrounding the outside of the core-shell structure. All liprotides can transfer their entire FA content to vesicles, releasing aLA as monomers and softening the lipid membrane. The more similar to OA, the more efficiently the different FAs induce hemolysis. We conclude that aLA can take up and transfer a wide variety of FA to membranes, provided they contain a cis-bond. This highlights liprotides as a general class of complexes where both protein and cis-FA component can be varied without departing from a generic (though sometimes multi-layered) core-shell structure.

AB - α-Lactalbumin (aLA) has been shown to form complexes with oleic acid (OA), which may target cancer cells. We recently showed that aLA and several other proteins all form protein-OA complexes called liprotides with a generic structure consisting of a micellar OA core surrounded by a shell of partially denatured protein. Here we report that a heat treatment and an alkaline treatment method both allow us to prepare liprotide complexes composed of aLA and a range of unsaturated fatty acids (FA), provided the FAs contain cis (but not trans) double bonds. All liprotides containing cis-FA form both small and large species, which all consist of partially denatured aLA, though the overall shape of the species differs. Small liprotides have a simple core-shell structure while the larger liprotides are multi-layered, i.e. they have an additional layer of both FA and aLA surrounding the outside of the core-shell structure. All liprotides can transfer their entire FA content to vesicles, releasing aLA as monomers and softening the lipid membrane. The more similar to OA, the more efficiently the different FAs induce hemolysis. We conclude that aLA can take up and transfer a wide variety of FA to membranes, provided they contain a cis-bond. This highlights liprotides as a general class of complexes where both protein and cis-FA component can be varied without departing from a generic (though sometimes multi-layered) core-shell structure.

KW - Cis fatty acids

KW - Disulfide bonds

KW - Liprotides

KW - Membrane interaction

KW - Small angle X-ray scattering

UR - http://www.scopus.com/inward/record.url?scp=84964800068&partnerID=8YFLogxK

U2 - 10.1016/j.bbapap.2016.04.003

DO - 10.1016/j.bbapap.2016.04.003

M3 - Journal article

C2 - 27068540

SN - 0006-3002

VL - 1864

SP - 847

EP - 859

JO - B B A - Proteins and Proteomics

JF - B B A - Proteins and Proteomics

IS - 7

ER -